Small proline-rich proteins 1 and 2 function as antimicrobial proteins in the skin

Human skin prevents the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to skin immunity is the sebaceous gland, yet our understanding of how sebocytes function in host defense is incomplete. Here we show that sebaceous glands respond to bacterial stimuli by generating small proline-rich proteins, SPRR1B and SPRR2A, which display bactericidal functions in skin. Further, LPS injected into mouse skin triggers the expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a. Both mouse and human SPRR proteins display potent bactericidal activity against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Thus, Sprr1a-/-;Sprr2a-/- mice are more susceptible to skin infection with these bacteria. Lastly, our findings demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. These findings provide insight into the regulation of SPRR proteins in skin and how the sebaceous gland contributes to host defense.